Coronary heart disease (CHD) is the leading cause of death in the United States, affecting 1 million people each year. The term cardiovascular vulnerable patient has been used to describe patients susceptible to acute coronary events based upon plaque, blood, or myocardial characteristics. Epidemiological studies have shown that stress is a significant and independent risk factor for patients with CHD, and also may be associated with increased cardiovascular vulnerability. This evidence has provided a rationale for developing stress management training (SMT) interventions for CHD patients. Although cardiac rehabilitation (CR) is regarded as integral to the care of patients with CHD, SMT is currently not an essential component of most CR programs. We believe that the therapeutic potential of SMT has remained unfulfilled due to a paucity of well- designed clinical studies in CHD patients. Because randomized clinical trials (RCTs) employing hard endpoints-death or myocardial infarction-require large samples followed over long time intervals, such approaches are generally not feasible for most psychosocial RCTs. This application was developed in response to Program Announcement (PA-07-322), which invited proposals to examine the efficacy of SMT in improving intermediate outcomes, defined by biomarkers of cardiovascular risk purported to be in the pathway through which mental stress is thought to influence clinical events. The study proposed in this application will build upon our previous work in which we demonstrated the feasibility and efficacy of SMT in cardiovascular patients with stable CHD. Specifically, we propose to (a) evaluate the effectiveness of SMT combined with exercise-based CR in reducing stress in vulnerable cardiac patients; (b) examine changes in intermediate endpoints, including measures of cardiac vagal control, vascular endothelial dysfunction, inflammation, platelet function, and mental stress-induced myocardial ischemia, which are recognized biomarkers of cardiac vulnerability to clinical CHD events; (c) explore potential moderators and mediators by which SMT may improve biomarkers of risk; and (d) determine the impact of SMT on clinical endpoints over a mean follow-up period of 30 months. One hundred fifty men and women with CHD will be randomly assigned to exercise- based CR or to SMT-enhanced CR. Before and after 3 months of treatment, patients will undergo clinical assessments of stress and biomarkers of cardiovascular risk. Follow-up assessments will determine the maintenance of benefit and document cardiac events. The data generated from this study will have important clinical significance by determining the extent to which SMT combined with exercise-based CR reduces stress and improves prognosis in vulnerable cardiac patients.